Mitrevski Milica, Marrapodi Ramona, Camponeschi Alessandro, Cavaliere Filomena Monica, Lazzeri Cristina, Todi Laura, Visentini Marcella
Department of Clinical Medicine, Sapienza University of Rome , Rome , Italy.
Department of Molecular Medicine, Sapienza University of Rome , Rome , Italy.
Front Immunol. 2015 Jan 22;6:4. doi: 10.3389/fimmu.2015.00004. eCollection 2015.
Intravenous immunoglobulin (IVIG) is used as replacement therapy in patients with antibody deficiencies and at higher dosages in immune-mediated disorders. Although different mechanisms have been described in vitro, the in vivo immunomodulatory effects of IVIG are poorly understood. Different studies have suggested that IVIG modulates B-cell functions as activation, proliferation, and apoptosis. Recently, it was shown that IVIG induces in vitro B-cell unresponsiveness similar to anergy. In accord with this, we recently reported that IVIG therapy in patients affected by common variable immunodeficiency (CVID) interferes in vivo with the B-cell receptor (BCR) signaling by increasing constitutive ERK activation and by reducing the phosphorylated ERK increment induced by BCR cross-linking. Moreover, we observed that IVIG induces in CVID patients an increase of circulating CD21(low) B-cells, an unusual population of anergic-like B-cells prone to apoptosis. Therefore, IVIG at replacement dose in vivo could prime B-cells to an anergic, apoptotic program. Here, we discuss these recent findings, which may improve our understanding of the immunomodulatory effects of IVIG, individualizing single involved molecules for more specific treatments.
静脉注射免疫球蛋白（IVIG）在抗体缺陷患者中用作替代疗法，在免疫介导的疾病中则使用更高剂量。尽管体外已描述了不同的机制，但IVIG的体内免疫调节作用仍知之甚少。不同的研究表明，IVIG可调节B细胞功能，如激活、增殖和凋亡。最近发现，IVIG在体外可诱导B细胞无反应性，类似于无反应状态。与此一致的是，我们最近报道，在患有常见可变免疫缺陷（CVID）的患者中，IVIG治疗通过增加组成性ERK激活和减少BCR交联诱导的磷酸化ERK增加，在体内干扰B细胞受体（BCR）信号传导。此外，我们观察到IVIG在CVID患者中诱导循环CD21（低）B细胞增加，这是一群易于凋亡的无反应样B细胞。因此，体内替代剂量的IVIG可能会使B细胞启动无反应、凋亡程序。在此，我们讨论这些最新发现，这可能会增进我们对IVIG免疫调节作用的理解，为更特异性的治疗确定单个相关分子。
